New developments in the management of relapsed/refractory multiple myeloma – the role of ixazomib

Abstract

Ixazomib is the first oral proteasome inhibitor to be approved, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was on the basis of results from the phase 3, double-blind, placebo-controlled TOURMALINE-MM1 study, which demonstrated a 35% improvement in progression-free survival with the all-oral combination of ixazomib plus lenalidomide–dexamethasone versus lenalidomide–dexamethasone alone (median: 20.6 vs 14.7 months; hazard ratio: 0.74, p=0.012; median follow-up 14.7 months). The addition of ixazomib to the lenalidomide–dexamethasone regimen was associated with limited additional toxicity and had no adverse impact on patient-reported quality of life. Common grade ≥3 adverse events with ixazomib include gastrointestinal adverse events, rash, and thrombocytopenia. Here, we review the efficacy, safety, pharmacokinetics, and patient-reported quality of life data seen with ixazomib, and discuss the role of this oral agent in the treatment of patients with relapsed/refractory multiple myeloma, including in patients with high-risk cytogenetic abnormalities and those with multiple prior therapies.

Keywords:

• ixazomib
• multiple myeloma
• proteasome inhibitor
• clinical
• efficacy
• tolerability
• pharmacokinetics

Acknowledgments

The authors acknowledge the writing support of Jane Saunders of FireKite, an Ashfield company, part of UDG Healthcare plc, in the development of this manuscript, which was funded by Millennium Pharmaceuticals, Inc., and complied with Good Publication Practice 3 ethical guidelines (Battisti et al, Ann Intern Med 2015;163:461-4).

Disclosure

PGR: Membership on an entity’s board of directors, speakers bureau, or its advisory committees: Takeda, Janssen. SK: Consultancy: Takeda, Celgene, Janssen, BMS, Noxxon, Kesios, Glycomimetics, Skyline; honoraria, Skyline Dx. JPL: Consultancy: Takeda and Novartis; research funding: Takeda, Novartis, Celgene. NG, DB, and HvdV: Employment: Takeda Pharmaceutical Company Limited. PM: Honoraria, BMS, Takeda, Janssen, Celgene, Novartis. The authors report no other conflicts of interest in this work.